MicroRNAs, inflammation, and acute lung injury.

MicroRNA、炎症和急性肺损伤。

• 批准号: 7990182
• 负责人: Gang Liu
• 金额: $ 18.31万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7990182
• 关键词: Acute; Acute Lung Injury; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Attenuated; Binding; Cardiovascular Diseases; Cells; Data; Development; Diabetes Mellitus; Disease; Distant; Equilibrium; Event; Functional RNA; Functional disorder; Gene Expression; Goals; Incidence; Infection; Inflammation; Inflammatory; Inflammatory Response; Invaded; Life; Liver; Lung; Malignant Neoplasms; Mediator of activation protein; MicroRNAs; Mus; Nucleotides; Organ; Outcome; Pathogenesis; Play; Population; Property; Reactive Oxygen Species; Regulation; Regulator Genes; Role; Severities; Small RNA; Subfamily lentivirinae; TLR4 gene; Therapeutic; Up-Regulation; Virus Diseases; chemokine; cytokine; improved; in vivo; intravenous administration; lung injury; macrophage; microorganism; monocyte; neutrophil; novel therapeutic intervention; prevent; promoter; public health relevance; response

DESCRIPTION (provided by applicant): MicroRNAs, a class of 21-22 nucleotide non-coding small RNAs, are important regulators of gene expression and have been shown to modulate a broad range of cellular and developmental events. We have found that the expression of miR147 is upregulated in LPS stimulated cells and miR147 has anti-inflammatory properties which diminish activation in macrophages. Our data therefore suggest that specific microRNAs participate in regulating acute TLR4 induced inflammatory events and that modulation of microRNAs may have potential therapeutic benefit in life-threatening inflammatory conditions, such as ALI. Our hypothesis is that miR147 participates in the regulation of acute inflammatory responses and play a major role in determining the development, perpetuation, and severity of ALI. Our specific aims are: 1) To characterize the role of miR147 in regulating TLR4 induced inflammatory responses by delineating the mechanisms leading to LPS induced upregulation in the expression of miR147, elucidating the role that miR147 occupies in modulating LPS induced cellular activation, and delineating the mechanisms through which miR147 affects LPS induced cellular activation. 2) To explore if modulation of the expression of miR147 attenuates LPS induced ALI by determining the expression of miR147 in the lungs of LPS treated mice and exploring if modulation of miR147 expression can attenuate LPS induced ALI. The proposed studies should not only improve understanding of cellular mechanisms leading to ALI, but also are likely to suggest novel therapeutic interventions aimed at decreasing the incidence and/or severity of ALI. PUBLIC HEALTH RELEVANCE: MicroRNAs are important regulators of many essential cellular and developmental events. Deregulations of microRNA expression have been shown to be involved in a number of diseases, such as cancer, cardiovascular diseases, and diabetes. However, whether microRNAs regulate acute inflammatory responses and acute inflammation related diseases, including acute lung injury (ALI) has not been elucidated. We found that the expression of miR147 is upregulated in LPS stimulated macrophages and mouse lungs and miR147 has anti-inflammatory activities. The studies proposed in this application should not only improve understanding of the roles of microRNAs in regulation of LPS induced inflammatory responses and acute lung injury, but also are likely to suggest novel therapeutic interventions aimed at decreasing the incidence and/or severity of acute lung injury.

描述（由申请人提供）：MicroRNA是一类21-22个核苷酸非编码小RNA，是基因表达的重要调节剂，已被证明可以调节广泛的细胞和发育事件。我们发现，MiR147的表达在LPS刺激的细胞中上调，MiR147具有抗炎特性，可减少巨噬细胞的激活。因此，我们的数据表明，特定的microRNA参与调节急性TLR4诱导的炎症事件，并且MicroRNA的调节可能在威胁生命的炎性疾病（例如ALI）中具有潜在的治疗益处。我们的假设是MiR147参与调节急性炎症反应，并在确定ALI的发展，永久性和严重性方面起着重要作用。 Our specific aims are: 1) To characterize the role of miR147 in regulating TLR4 induced inflammatory responses by delineating the mechanisms leading to LPS induced upregulation in the expression of miR147, elucidating the role that miR147 occupies in modulating LPS induced cellular activation, and delineating the mechanisms through which miR147 affects LPS induced cellular activation. 2）探索MIR147表达的调节是否通过确定MiR147在LPS处理的小鼠的肺中的表达来减轻LPS诱导的ALI，并探索MIR147表达的调节是否可以减弱LPS诱导的ALI。拟议的研究不仅应提高对导致ALI的细胞机制的理解，而且还可能提出旨在降低ALI发病率和/或严重性的新型治疗干预措施。 公共卫生相关性：microRNA是许多基本细胞和发育事件的重要调节因子。 MicroRNA表达的不含量已显示出与多种疾病有关，例如癌症，心血管疾病和糖尿病。但是，尚未阐明microRNA是否调节急性炎症反应和急性炎症相关疾病，包括急性肺损伤（ALI）。我们发现MiR147的表达在LPS刺激的巨噬细胞和小鼠肺中被上调，而MiR147具有抗炎活性。本应用中提出的研究不仅应提高对MicroRNA在LPS调节炎症反应和急性肺损伤中的作用的理解，而且还可能表明旨在降低急性肺损伤的发生率和/或严重程度的新型治疗干预措施。